Recruiting participants for clinical trials in low- and middle-income countries (LMICs) is no small feat—it’s a complex dance of urgency, trust, and collaboration. But here’s where it gets controversial: while the need for vaccines in LMICs is undeniable, the process of engaging communities in trials often raises ethical and logistical questions that many overlook. Let’s dive into why this matters and how it’s being tackled, using the development of the M72 tuberculosis (TB) vaccine as a case study.
By Alemnew Dagnew, Head of Vaccine Development, Gates Medical Research Institute (Gates MRI)
Conducting clinical trials in LMICs differs drastically from doing so in the United States or Europe. One of the most striking differences lies in participant recruitment. In LMICs, the high burden of infectious diseases like TB creates a palpable sense of urgency. For instance, TB remains the world’s deadliest infectious disease, claiming over 1.2 million lives in 2023 alone. With an estimated 10.8 million cases that year, it’s not uncommon for people in LMICs to know someone personally—a family member or neighbor—who has battled TB. This personal connection often fuels a strong motivation to participate in vaccine trials.
At Gates MRI, our work on global health threats like TB and malaria is driven by this urgency. However, we must approach recruitment with respect and care. It’s not just about signing up participants; it’s about ensuring communities understand the trial’s goals and how they can contribute meaningfully. And this is the part most people miss: successful recruitment isn’t just a numbers game—it’s about building trust and fostering long-term partnerships.
Why Recruitment is the Backbone of Clinical Trials
Despite its devastating impact, TB has only one vaccine—BCG—which has been in use for over a century. While BCG protects young children from severe forms of TB like meningitis, it offers little defense against pulmonary TB in adolescents and adults, who bear the brunt of the disease and are its primary transmitters. At Gates MRI, we’re developing the M72 vaccine to address this gap. Our largest trial to date, the M72 Phase 3 trial, spans 54 sites across Indonesia, Kenya, Malawi, South Africa, and Zambia, with a recruitment target of 20,000 participants. Remarkably, we reached this goal 11 months ahead of schedule by focusing on three key strategies.
1. Mapping Hotspots: The Unseen Prep Work
TB disproportionately affects LMICs, so it’s logical to conduct trials where the disease burden is highest. But running large-scale trials in these settings is challenging. To meet timelines, you need a massive sample size and well-prepared clinical sites. This is where epidemiology studies come in. Before the M72 trial, we conducted a thorough study across 14 countries and 45 sites to identify TB hotspots and prepare sites. By collecting and evaluating samples for TB infection, we pinpointed high-burden areas, ensuring we could reach the trial’s statistical milestones efficiently.
Here’s the controversial part: some argue that focusing solely on hotspots exploits vulnerable populations. But is it exploitation, or is it a necessary step to accelerate solutions for those most affected? We invite your thoughts in the comments.
2. Building Trust Through Community Engagement
Recruitment isn’t just about filling slots—it’s about building relationships. For the M72 trial, we engaged a global community advisory board comprising TB experts and civil society leaders. Their feedback shaped our strategy, ensuring it aligned with local needs. At the site level, community advisory boards (CABs) played a pivotal role in addressing concerns and fostering shared ownership of the research. This approach isn’t just ethical—it’s practical. Without trust, even the most well-designed trial can falter.
3. Leveraging Local Expertise and Partnerships
Collaboration with local healthcare providers, such as TB clinics, was essential for reaching high-burden communities. Our pre-trial epidemiology study not only identified hotspots but also tested and improved local infrastructure, from sample processing to shipping. This hands-on experience prepared sites for the Phase 3 trial, ensuring smoother operations.
The Bigger Picture: Trials as Community Collaborations
Clinical trials don’t exist in isolation. Recruitment is the starting point for a partnership that lasts beyond the trial’s end. By involving communities in every step—from design to execution—we not only ensure ethical research but also increase the likelihood of success.
But here’s a thought-provoking question: As we rely more on community engagement, how do we balance local input with scientific rigor? Where do we draw the line between adaptation and compromise?
About the Author:
Alemnew Dagnew, MD, MSc, MPH, leads vaccine and biologics development at Gates MRI, focusing on diseases like TB that disproportionately affect underserved populations. His work spans vaccine licensure and international clinical trials, with oversight from regulatory bodies like the U.S. FDA, EMA, and Health Canada. Learn more at Gates MRI.
